Physics and Evolution of Biological Macromolecules

Allostery in Its Many Disguises: From Theory to Applications

Published date : 01 Apr 2019

Allosteric regulation plays an important role in many biological processes, such as signal transduction, transcriptional regulation, and metabolism. Allostery is rooted in the fundamental physical properties of macromolecular systems, but its underlying mechanisms are still poorly understood.

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Journal Paper
journal
Structure 27, 2019 Jan 17. pii: S0969-2126(19)30003-6. doi: 10.1016/j.str.2019.01.003
Impact Factor
4.907

Toward Comprehensive Allosteric Control over Protein Activity

Published date : 28 Feb 2019

Universality of allosteric signaling in proteins, molecular machines, and receptors complemented by the great advantages of prospected allosteric drugs in the highly specific, non-competitive, and modulatory nature of their actions calls for deeper theoretical understanding of allosteric communication. We present a computational model that makes it possible to tackle the problem of modulating the energetics of protein allosteric communication.

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Journal Paper
journal
Structure 27, Pg 1-13, May 7, 2019, doi: 10.1016/j.str.2019.01.1016
Impact Factor
4.907

Exploring chromatin hierarchical organization via Markov State Modelling

Published date : 31 Dec 2018

We propose a new computational method for exploring chromatin structural organization based on Markov State Modelling of Hi-C data represented as an interaction network between genomic loci. A Markov process describes the random walk of a traveling probe in the corresponding energy landscape, mimicking the motion of a biomolecule involved in chromatin function.

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Journal Paper
journal
PLoS Computational Biology, 2018 Dec 31;14(12), doi: 10.1371/journal.pcbi.100668
Impact Factor
3.955

Simple yet functional phosphate-loop proteins

Published date : 30 Nov 2018

Abundant and essential motifs, such as phosphate-binding loops (P-loops), are presumed to be the seeds of modern enzymes. The Walker-A P-loop is absolutely essential in modern NTPase enzymes, in mediating binding, and transfer of the terminal phosphate groups of NTPs. However, NTPase function depends on many additional active-site residues placed throughout the protein’s scaffold. Can motifs such as P-loops confer function in a simpler context?

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Journal Paper
journal
Proceedings of the National Academy of Sciences of the United States of America, PNAS, doi: 10.1073/pnas.1812400115
Impact Factor
9.504

On the perturbation nature of allostery: sites, mutations, and signal modulation

Published date : 12 Nov 2018

Regardless of the diversity of systems, allosteic signalling is found to be always caused by perturbations. This recurring trait of allostery serves as a foundation for developing different experimental efforts and theoretical models for the studies of allosteric mechanisms. Among computational approaches considered here particular emphasis is given to the structure-based statistical mechanical model of allostery (SBSMMA), which allows one to study the causality and energetics of allosteric communication.

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Journal Paper
journal
Current Opinion in Structural Biology, Vol. 56, June 2019, Pg 18-27, doi: 10.1016/j.sbi.2018.10.008
Impact Factor
7.179

AlloMAPS: allosteric mutation analysis and polymorphism of signaling database

Published date : 26 Oct 2018

AlloMAPS database provides data on the causality and energetics of allosteric communication obtained with the structure-based statistical mechanical model of allostery (SBSMMA). The database contains data on allosteric signaling in three sets of proteins and protein chains: (i) 46 proteins with comprehensively annotated functional and allosteric sites; (ii) 1908 protein chains from PDBselect set of chains with low (<25%) sequence identity; (iii) 33 proteins with more than 50 known pathological SNPs in each molecule.

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Journal Paper
journal
Nucleic Acis Research, 2018, Oct 26, doi:10.1093/nar/gky1028
Impact Factor
11.561

Reversing allosteric communication: From detecting allosteric sites to inducing and tuning targeted allosteric response

Published date : 18 Jun 2018

The omnipresence of allosteric regulation together with the fundamental role of structural dynamics in this phenomenon have initiated a great interest to the detection of regulatory exosites and design of corresponding effectors.

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Journal Paper
journal
PLoS Computational Biology, 18 Jun 2018, doi:10.1371/journal.pcbi.1006228
Impact Factor
3.955

Insulin-Degrading Enzyme in the Fight against Alzheimer's Disease

Published date : 29 Nov 2017

After decades of research and clinical trials there is still no cure for Alzheimer's disease (AD). While impaired clearance of amyloid beta (Aβ) peptides is considered as one of the major causes of AD, it was recently complemented by a potential role of other toxic amyloidogenic species. Insulin-degrading enzyme (IDE) is the proteolytic culprit of various β-forming peptides, both extracellular and intracellular.

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Journal Paper
journal
Trends in Pharmacological Sciences, 10 Nov 2017, doi : 10.1016/j.tips.2017.10.008
Impact Factor
12.797

AlloSigMA: Allosteric Signalling and Mutation Analysis server

Published date : 06 Jul 2017

Motivation: Allostery is an omnipresent mechanism of the function modulation in proteins via either effector binding or mutations in the exosites. Despite the growing number of on-line servers and databases devoted to prediction/classification of allosteric sites and their characteristics, there is a lack of resources for an efficient and quick estimation of the causality and energetics of allosteric communication.

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Journal Paper
journal
Bioinformatics, 2017, doi: 10.1093/bioinformatics/btx430
Impact Factor
7.307